Replication

Before a cell divides it has to
replicate its DNA so that the daughter cell receives
a copy of the genome. The DNA helix consists of two
complementary DNA strands. Therefore, each of the two
strands serves as a template for the
construction of the other strand. Under normal
conditions the DNA is packed into a compact structure
called chromatin. To be able to replicate, the cell
has to unfold and unwind the DNA, and also has to
separate the two strands from each other. The cell
has a complex machinery to perform these tasks. When
it is time to replicate, special initiator proteins
attach to the DNA at regions called replication
origins. These regions are characterised by a weak
bond between the two DNA strands. There are around
10,000 replication origins on the DNA in a cell; this
arrangement increases the rate of replication
tremendously. The initiator proteins pry the two
strands apart and a small gap is created at the
replication origin. Once the strands are separated
another group of proteins, that carry out the DNA
replication, attaches and go to work.

This group of proteins includes
helicase, which serves as an unzipper by breaking the
bonds between the two DNA strands. This unzipping
takes place in both directions from the replication
origins, creating a replication bubble. The
replication is therefore said to be bi-directional.
Once the two strands are separated a small piece of
RNA, called an RNA primer, is
attached to the DNA by an enzyme called DNA
primase. These primers are the beginnings of all new
DNA chains since the enzyme responsible
for the copying of the DNA, DNA polymerase, can not
start from scratch. It is a self-correcting enzyme and copies
the DNA template with
remarkable fidelity.

The DNA polymerase can only
read in the 3' to 5' direction. This gives rise to
some trouble since the two strands of the DNA are
antiparallel. On the upper strand which runs from 3'
to 5', nucleotide
polymerisation can take place continuously without
any problems. This strand is called the leading
strand. But how does the polymerase copy the other
strand then when it runs in the opposite direction,
from 5' to 3'? On this so called lagging strand the
polymerase produces short DNA fragments, called
okazaki fragments, by using a backstitching
technique. These lagging strand fragments are primed
by short RNA primers and are
subsequently erased and replaced by DNA.